Transcriptomic Profiling of zygotes in Mice Lacking the Insulin Receptor-Related Receptor

Acid-base homeostasis is a fundamental regulator of ovarian physiology, influencing follicular development, oocyte maturation, and hormone synthesis. Disruption of local pH balance within the ovarian microenvironment can impair steroidogenesis, fertilization, and early embryo viability. The insulin receptor-related receptor (IRR) is a unique member of the insulin receptor's family that functions as a sensor of extracellular alkaline pH, becoming activated when the surrounding environment exceeds pH 7.9. IRR expression is highly tissue-specific, detected primarily in kidney collecting ducts, stomach, specific regions of the brain and the ovary. In mice with a knockout of the insrr gene, which encodes for IRR, urinary bicarbonate secretion in response to alkali loading is impaired. However, its mechanisms of action and physiological significance in non-renal organs, particularly within the female reproductive system, are unknown. To address this issue, we analyzed and compared the zygotes transcriptomes of wild-type and insrr knockout mice. We found 28 transcripts with significant changed expression levels in zygotes. In preimplantation embryos changed 13 protein-coded genes (Cnpy3, Nkx2-1, Fau-ps1, Nedd9, Cyp2e1, Ccdc184, Vmn2r-ps19, Emc6, Pcdhb16, Fam91a1, Zfp988, Rnf11, Nkap) and several RNA coded genes (Gm25846, Gm28016, Gm35453, Gm28361, Gm9924, Gm42949, Gm37698, Gm37377, Gm6850, Gm6590, AC125455.1, Gm7132, 1010001B22Rik, Gm42672, Gm25188).